2007 Fiscal Year Final Research Report Summary
Synthetic studies for functional elucidation of RNA catalysis and H4 receptor
| Project/Area Number |
16590024
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
HARUSAWA Shinya Osaka University of Pharmaceutical Sciences, 薬学部, Prof. (90167601)
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| Co-Investigator(Kenkyū-buntansha) |
YAMATODANI Atsushi Osaka University, Faculty of Medicine, Prof. (30116123)
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| Project Period (FY) |
2004 – 2007
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| Keywords | ribozyme / imidazole / C-nueleoside / phosphoramidite / histamine / H_3 / H_4 / antagonist |
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| Research Abstract |
A novel C4-linked imidazole ribonucleoside phosphoramidite was designed and synthesized. This phosphoramidite was successfully incorporated the imidazole moiety into VS and hairpin ribozymes. As the modified imidazole ribozymes thus obtained indicated the activities in both cleavage and ligation, the data provided good evidence for general acid-base catalysis by their natural nucleobases. Further, the second stable imidazole ribonucleoside phosphoramidite has designed and synthesized bearing a cyanoethyl group as a protective group at 2'-OH group.
On the other hand, novel histamine H_3 antagonists having two chiral centers and stable chair conformations were designed and synthesized. Among them, a (2S,2R)-N-alkyl derivative (OUP-153), which increased histamine release to 180-200% of basal levels, was found as a novel histamine H_3 antagonist. In addition, S-alkyl-N-alkylisothioureas were efficiently synthesized via a synthetic approach using 3-phenylpropionyl isothiocyanate (PPI). The utility of the approach was proved by the synthesis of clobenpropit, a potent H_3 antagonist and its analogues.
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